The present invention relates to compositions comprising polynucleotides that specifically bind to a target protein and to methods for extending the half-life of such polynucleotides in vivo. The compositions are complexes, either covalent or non-covalent, of the polynucleotide and a protein (other than the target protein). The complexes typically include the 5xe2x80x2 or 3xe2x80x2 end or both of the polynucleotide.
Aptamers are nucleic acid sequences that specifically bind to target proteins and other biomolecules (16,30). Aptamers are of interest for imaging, therapy and radiotherapy applications, and they are a unique way to use nucleic acids.
The present invention is embodied partly in complexes of aptamers with a protein. Complexation of the aptamer with a protein greatly increases the half-life of the aptamer in vivo. The complexes can be non-covalent or covalent. Non-covalent complexes can be formed by covalent attachment of a ligand to the nucleic acid and then complexing the ligand with its specific binding protein.
The aptamer can be one that specifically binds to thrombin. Such aptamers be labeled for detection outside the body and then can be used in methods for imaging blood clots (thrombi) in vivo. In unlabeled form, such aptamers can also be used for inhibiting or preventing coagulation of blood. One problem with such methods is that the half-life of aptamers in serum is typically very short. By complexing the aptamer with a protein (other than the target aptamer binding protein) the half-life of the aptamer in serum is greatly increased. Thus, the present invention provides in vitro methods for imaging thrombi and for inhibiting blood coagulation.